Combined Antiretroviral Therapy (cART) During Pregnancy>

There are two goals of cART during pregnancy. The first goal is to reduce maternal viral load below the limit of detection throughout pregnancy in order to sustain her immune system and controls opportunistic infection. The second goal is to reduce the risk of mother to child transfer (MTCT) by lowering maternal antepartum viral load and providing infant pre- and postexposure prophylaxis.

Pregnancy presents clinical issues that may require specialized OB/HIV care, including:

Patient counseling prior to cART should include:

Beginning therapy:

Combined Antiretroviral Therapy is recommended for all HIV+ pregnant women regardless of CD4 count and viral load. Current recommendations for beginning antiretroviral therapy are similar to those for a non-pregnant individual. In general, it is recommended that pregnant women who are starting therapy for their own health be treated as soon as possible, including in the first trimester. For women who are beginning therapy only to prevent mother-to-child transmission, delaying cART until after the first trimester can be considered. Regardless of the recommendations, a women's informed decision to use, refuse or delay cART must be respected.

Safety of antiretroviral drugs during pregnancy:

Beginning in January 2018, VESTED investigators randomly assigned 643 women to begin HIV treatment 14-28 weeks into their pregnancies with EFV/FTC/TDF or two newer regimens: DTG+FTC/TAF and DTG+FTC/TDF. EFV/FTC/TDF is formulated as a single tablet, while the newer regimens each consist of a DTG tablet taken with a combined FTC/TAF or FTC/TDF tablet.

The researchers found that nearly 98% of women who received either of the DTG-containing regimens were virally suppressed at the time of delivery, meaning their viral load (amount of HIV in the blood) was undetectable using standard tests. In contrast, 91% of women who received EFV/FTC/TDF were virally suppressed at delivery. Two infants, one in each of the groups that received DTG-containing regimens, were diagnosed with HIV within 14 days of birth. Researchers are currently investigating data on medication adherence and drug levels at the time of delivery.

The researchers found that 24% of women taking DTG+FTC/TAF had an adverse pregnancy outcome compared with 33% of women taking DTG+FTC/TDF or EFV/FTC/TDF. While these rates are high, they are consistent with adverse pregnancy event rates in low- and middle-income countries, where most participants live. These outcomes included pregnancy complications of preterm delivery, low infant birth weight based on gestational age (a measure of the age of a pregnancy which is taken from the beginning of the woman's last menstrual period), and stillbirth. 

Together, these findings show that while all three regimens are safe and effective in pregnancy, HIV is better controlled by DTG-containing regimens, and DTG+FTC/TAF may lead to lower adverse pregnancy outcomes. The findings affirm WHO recommendations for use of DTG in pregnant women (DHHS 2020).

Pregnancy
Panel's Recommendations for the Use of Antiretroviral Drugs During Pregnancy
  • When choosing an antiretroviral (ARV) drug regimen for a pregnant woman, providers and patients should consider multiple factors, including adverse effects, drug interactions, pharmacokinetics (PKs), convenience of the individual drugs and drug combinations in the regimen, available pregnancy safety and outcome data, and the patient’s resistance test results and comorbidities.
  • The same regimens that are recommended for the treatment of nonpregnant adults should be used in pregnant women when sufficient data suggest that appropriate drug exposure is achieved during pregnancy; clinicians should weigh the risks of adverse effects for women, fetuses, or infants against the benefits of these regimens and recognize that there are often incomplete data on the safety of ARV drugs in pregnancy. For more information, see Tables 4 and 5.
  • In most cases, women who present for obstetric care on fully suppressive ARV regimens should continue their current regimens.
  • PK changes in pregnancy may lead to lower plasma levels of some ARV drugs and necessitate increased doses, more frequent dosing, boosting, more frequent viral load monitoring, or a change in ARV regimen; see Pregnant Women with HIV Who Are Currently Receiving Antiretroviral Therapy.
  • The Panel emphasizes the importance of counseling and informed decision-making regarding all ARV regimens for people with HIV. For additional information, see Preconception Counseling and Care for Women of Childbearing Age with HIV, Teratogenicity, Appendix C: Antiretroviral Counseling Guide for Health Care Providers, and Tables 4 and 5.
  • After delivery, clinicians should discuss reproductive desires, the risks and benefits of conceiving on the current ARV regimen, and contraceptive options. See Preconception Counseling and Postpartum Care for more information.
  • Folic acid is known to prevent neural tube defects in the general population. All pregnant women and women who might conceive should take at least 400 mcg of folic acid daily ). 
Preferred Dual-NRTI Backbones
ABC/3TC Available as an FDC. Can be administered once daily. ABC should not be used in patients who test positive for HLA-B*5701 because of the risk of developing a hypersensitivity reaction. ABC/3TC administered with ATV/r or EFV is not recommended if pretreatment HIV RNA is >100,000 copies/mL.
TDF/FTC
or
TDF/3TC		 TDF/FTC is available as an FDC. Either coformulated TDF/FTC or separate doses of TDF and 3TC can be administered once daily. TDF has potential renal toxicity; thus, TDF-based, dual-NRTI combinations should be used with caution in patients with renal insufficiency.
Preferred INSTI Regimens
DTG/ABC/3TC (FDC)
or
DTG plus a Preferred Dual-NRTI Backbonea		 Administered once daily. The use of DTG/ABC/3TC requires HLA-B*5701 testing, because this FDC contains ABC. INSTI-based regimens may be particularly useful when drug interactions or the potential for preterm delivery with a PI-based regimen are a concern. In nonpregnant adults, DTG is associated with lower rates of INSTI resistance than RAL; like RAL, DTG has been shown to rapidly decrease viral load in ARV-naive pregnant women who present to care later in pregnancy. DTG is Preferred for the treatment of pregnant women with acute HIV infection and for women who present to care late in pregnancy. There are specific timing and/or fasting recommendations if DTG is taken with calcium or iron (e.g., in prenatal vitamins; see Table 10). The use of DTG at conception and in very early pregnancy has been associated with a small, but statistically significant, increase in the risk of NTDs; this information should be discussed with patients to ensure informed decision-making. For more information, see Recommendations for Use of Antiretroviral Drugs During Pregnancy, Table 5, Teratogenicity, and Appendix C: Antiretroviral Counseling Guide for Health Care Providers. 
RAL plus a Preferred Dual-NRTI Backbone PK data are available for RAL in pregnancy when using the twice-daily formulation (400 mg twice daily), but data are not available for the once-daily 1,200 mg (2 x 600 mg) extended-release formulation “raltegravir HD”. Twice-daily dosing is required in pregnancy. RAL has been shown to produce rapid viral load decline to undetectable levels in women who present for initial therapy late in pregnancy. INSTI-based regimens may be particularly useful when drug interactions or the potential for preterm delivery with PI-based regimens are a concern. There are specific timing and/or fasting recommendations if RAL is taken with calcium or iron (e.g., in prenatal vitamins; see Table 10).
Preferred PI Regimens
ATV/r plus a Preferred Dual-NRTI Backbone Once-daily administration. Extensive experience with use in pregnancy. Maternal hyperbilirubinemia; no clinically significant neonatal hyperbilirubinemia or kernicterus reported, but neonatal bilirubin monitoring is recommended. Cannot be administered with PPIs. Specific timing recommended for dosing with H2 blockers (see Table 10).
DRV/r plus a Preferred Dual-NRTI Backbone Better tolerated than LPV/r. Experience with use in pregnancy is increasing. Must be used twice daily in pregnancy.

Reducing Mother to Child Transmission (MTCT):

Ideally, antepartum cART will suppress maternal HIV plasma levels to "undetectable" during pregnancy. Several studies indicate that Cesarean delivery prior to labor and rupture of membranes significantly reduces perinatal transmission of HIV. Finally, breast feeding is a known mode of transmission and should be avoided.

 

References

U.S. Department of Health and Human Services. (2020, March 11). Newer anti-HIV drugs safest, most effective during pregnancy. National Institutes of Health. https://www.nih.gov/news-events/news-releases/newer-anti-hiv-drugs-safest-most-effective-during-pregnancy.